The primary objective of this research proposal is to examine the effects of selected combination chemotherapeutic regimens on the neoplastic transformation in preneoplastic mammary tissues. Two model systems will be examined: 1) established non-immunogenic and immunogenic preneoplastic outgrowth lines and 2) primary HAN occurring in BALB/cfC3H female mice. The frequency and rate of tumor formation will be assessed after treatment of the host mice with methotrexate, cytoxan, 5-FU, prednisone, bleomycin and a variety of other drugs. The ultimate aim of these experiments is to determine drug regimens which inhibit both neoplastic growth and neoplastic transformation.